Carbinol amines



I not the primary amine, groupsr-in tertiarya minoalkylanii nes ilnitedstates Paton ,t 2,946,793 CARBINOL AMnvEsf Raymond J. Micha'els, 'Jr., Mundelein, and-Harold Zaugg, Lake Forest, 111., assignors to AbbottLabora: tories, NorthChicago; 111., a corporation of Illinois No Drawing; Filed Sept.,25,"1 957i, Set-No. 8 ,014 p 7' Claims. 01. 260-268) This invention relates to a new series of carbinol amines and to novel methods of preparing same. The compounds of this invention are represented tby the following structural formula:

here R is hydrogen oralower alkyl group, Q-Attached to 'the Nare various aliphatic.,alkylan ino-.groups,iN= heterocyclic, substituted alkyl and the like, The alkylene carbon chain of such alkylamino grduPs repre sented by R which may be straight orbranchd. Y 'p- 3 resents I N- heterocyclic rings and "secondary and tertiary amines which are linked to the carbon chain throughan Among the secondary and tertiary janiines, can be listed reprmentative groups such as dimethylamino, diethylamino, methylamino and the like. Representative N- heterocyclic rings are py'rrolidine, piperidine," cyclohexylamine, piperazine, morpholine, pyridine, 'pyrazinel and the like. Lower alkyl -substituents on the N heterocyclic rings are also: included in the roup of amines represented by thesymbol Y as, for example, ZQS -dimethyI morpholine, 3,5-rnethylpiperazine'and the like. i t The compounds are preparedjrb'y reacting l diphenylr ethyleneoxide .i

with primary and secondary amine groups compr sl g' a portion-of alkyl' di'aminecompounds." "In this riianner,

such as 'dimethyla'minoethylamine," diethyl'aminoetliyl, I amine," dimethylaminopropylarnine', l-rmethy-l 4 I ethyl"; aminopiperazine, Nfi-aminoethylpiperidine; 2-dimethy-l-' amino-Z-methylpropylamine and the like participate in aminoalkylamine derivatives of l,l-diphenylethylene oxide. The foregoing primary amine groups in the listed compounds produce. derivatives where R is H in the; skeletal chemical structure as presented hereinbefore;

Reacting l,l diphenylethylene rnride with tertiary-' aminoalkyl secondary amine compounds provides tertiaryaminoalkylamine derivatives of fi substituted derivatives of a -diphenylethanol where R is a lower alkyl and X is N in the chemical structure :represenfing'the novel 760 the reaction with l,l-diphenylethylene' oxidetogive the 1 Y W. t O 1C6 methylamine ,1N:methyl N'-methyl ethylenediamine, tlilike. i Salts of the foregoing compounds, are'prepared and r are intended to comprise a part of this invention. By 5 the term saltsfv itintended thlat theyinclude acid addition salts oi-s'aid compounds, as well as the quaternary ammonium salts formed at the tertiary nitrogen in the a amineportion' of the instant compounds.

Ihe'compounds of this invention have been found to show antispasmodic. activity and antiarkinson activit'y/ The following examples are intended to serve as an illustrationiof the workings of invention and are not intended to' limit the products and steps to the exact ingredients and proportionsstated therein. 7

" EXAMPLEI N,N-dimethyl-N-(,B,fl-diphenyl-B-hydroxyethyl) propylenediamine l,l-diphenylethylene oxide (2.9 gins, .015 mole) is added portionwise to 3-dimethylaminopropylamine (4.6 gms, -.045' mole) and the resulting mixture is heated for 16 hours on the steam "bath. About 50 cc. otwater is, added to the cooled reaction mixture to precipitate the crude oily product.- Theproduct isextracted with ether and the extract isdried-.over anhydrous sodium sulfate. t f

'The drying agent is removed by. filtration andthe ether is evaporated to isolate the; product, N,N-dimethyl- 'N'--.(efi-dir rylrrhrd xrsthr )t-pr pr n ia in 1 The 30 product is taken up in 30' cc. of isopropyl alcohol and excess isopropyl alcoholic' hydrogen chloride, irom Q "which the di-hydrochloride salt of N,N-dimethyl-N' (fi,fldiphenyl-B-hydroiiyethyl) propylenediami'neis precipitated ina yield oft46%,' M.P. 274-249 C.

y s- Calcd. C H N O'2HCl: H, 7.60%; N, 7.55%.. Found: C, 61.78%; H, 7.48%; N, 7.44%. r

pie) and thereaction is conducted according to the procedure of Eiiz'arriplel. V

The M.P. of the'dihydrochloride salt oftthe above named diamine is 218-950 n litis oollected in a yield "drea s-.3192.

Anal st-home.- .fa o n N o-gnol; v 62.33%

in 7 -2;6 dim y (fifir bh lfi lm y I 1: .-prb'pyl)- niorpholin' i jlgl diphenylethyleneloxide (2.0, gms, Y ,or in is "amine (3.4 gmsl, .OZ'niole') and'rhe reaction is'conducted according to the procedure of Example I. a

The M.P. of the dihydroehloride salt of the above named amine 'i*s 1-7 2--3 C(a'nditj collected in ayie'ld oflLS gms. V A rgalysisr oalcdr for C H N O ZHCI: C, 62.58%; iH, 7'. 76%; N, 6f.35%. F0und:IC ,l62.36% H, 8.04%; 567 V V f EXAMPLE: 1v

(2.6 gms., .03 mole) and the reaction is conducted ace Found: C, 60.86%; H, 8.04%;N, 6.54%; Cl, 16.67%;

cording to the procedure of Example I.

"The M.P. o'fflthe-"dihydrochloride salt of the above named diamine is 217-8- C. and it is collected in a yield of 3.4 gms, 63%.

Analysis.Calcd. for C H N O-2HCl; C, 60.50%; H, 7.34%; N, 7.84%. Found; C, 61.16%; H, 7.23%; N, 7.83%.. g r 'x EXAMPLE VI v N,N,N--trim-ethyl-N-(5,;8-diphenyl-p-hydroxyethyl) ethylenediamine 1,1-diphenylethylene oxide (2.9 gms., .015 mole) is combined with 'dimethylaminoethyl methylamine' (3.1 gins, .03 mole) and the reaction is conducted according to the procedure of Example I.

- The M.P. of the dihydroehloride salt of the above o,,H;,N,o-2Hci=- c, 61.45%; V 7.55%. Found: o, 51.43%; H, 7.61%;

The M.P-. of the dihydrochloride salt of the'above named amine is 284 5? C. and it is collected in a yield of 3.5 gms.

Analysis.-Calcd. for C H N O-3HCl; C, 57.08%; H, 7.40%; N, 9.08%; CI, 22.98%; 0, 3.46%. Found: C, 57.29%; H, 7.47%; N, 9.08%;'Cl, 22.98%; O,.3.50%

combined With 2-pyrrolidylethylamine (3.4 gins, .03 pynolidine,

mole) and the reaction is conducted according to the procedure of Example I.

The M.P. of the dihydrochlorid e salt of. the above named amine is'235e-6", C. and it is'collected in a yield of 2.2 gms.

Analysis.--Calcd. for C H N O- 2 HC1; C, 62.66%; H, 7.36%; N, 7.31%. Found: C, 62.75%; H, 7.22%;1N,

EXAMPLE-IX 1-(pfi-diphenyl-p-hydroxyethyldmino) 2-dimethylarnino- Z-m ethylpropane 4 EXAMPLE x N -diethyl-N 3,5-diphenyl-fl-hydroxyethyl propylenediamine 1,1-diphenylethylene oxide (2.9 gms., .015 mole) is combined with a-diethylaminopropylamine (3.9 gms, .03

mole) and the reaction is conducted according to the procedure of Example I.

The M.P. of the dihydrochloride salt of the above named diamine is l523 C. and it is collected in a yield of 2.2 gms.

Analysis.--Ca1cd. for C H N O-2HCbH O: C, 60.43%; H, 8.21%; N, 6.71%; Cl, 16.99%; 0, 7.66%.

EXAMPLE XI N -dimethyl-N 5,5-diphenyl-fl-hydroxyethyl V ethylenediamine 1,1-diphenylethylene oxide (3.3 gms, .017 mole) is added portionwise to dimethylaminoethylamine (4.5 gms, .051 mole). A clear solution is formed and the mixture is then heated on a steam bath for 18 hours. After the reaction mixture is cooled, the oilyproduct solidifies.

This crude product is recrystallized 3 times from Skelly B to a constant M.P. of 934 C. The wt. of the product is 2 /2 gms., 52% yield.

Analysis.-Calcd. for C18H24N30I C, H,

8.51%; N, 9.85%. Found; C, 75.59%; H, 8.29%; N,

I 5 7 EXAMPLE XII I -(ppdiphanyl-p hydroxyethylaminaethyl) -'piperidine 1,1-dipheny1ethylene oxide (2.9 gms., .015 mole) is added portionwise to N-fi-aminoethylpiperidine (3.8 gms., .03 mole) containing .4 drops of Water. The mixture is heated for 18 hours on a steam bath. After the reaction mixture is cooled, the crude product solidifies.

This base is recrystallized 3 times from pentane to a constant M.P. of 57-8 C. The wt. of the obtained product is 1.5 gms. Analysis..Calcd.. for 'C H N O: C, 77.73%; H, 8.70%; N, 8.64%. Found: C, 78.04%;H, 8.85%; N,

Others may practice the invention in any of the numerous ways which will be suggested by this disclosure to one skilled in the art. All such practice of the invention is considered to be a part hereof provided it falls within the scope of the appended claims. I

We claim:

l. N,N dimethyl N (5,5 diphenyl 5 hydroxyethyl) ethylenediamine. I

2. N (5,18 diphenyl 5 hydroxyethylaminoethyl) '3. 1 -.methyl 4 (5, 3 diphenyl B hydroxyethylaminoethyl) -pipera zine.

4. N,N dimethyl N 6,3 diphenyl ,3 hydroxyethyl) propylenediamine. e I

.; s. N,N,N' trimethyl N. as diphenyl a .1...

droxyethyl) ethylenediamine. V

f A-'compdund represented by the structural formula:

WOH' lower alkyl 2-CHr-NHIower alkylend-N lower alkyl 7. A compound selected from the group consisting of bases represented by 1 I on where kis selected the group consisting of:

gen and lower alkyl; R isanalkylene group consisting of 1 to 4 carbon atoms and'Y is a substituent containing an N atom through which a" linkage is made 10 K and r is selected from the group consisting of monoalkylamino, diloweralkylamino, piperidino, morpholino, pyrrolidino and dialkylmorpholino and the non-toxic, acid addition salts thereof.

6 References Cited in the file of this patent UNITED STATES PATENTS 2,575,122 Pollard et a1. Nov. 13, 1951 2,600,217 Denton et a1 June 10, 1952 FOREIGN PATENTS 7 740,879 Germany Nov. 2, 1943 

7. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF BASES REPRESENTED BY 